Perfluorinated carboxylic acids (PFAs) represent derivatives of naturally occurring compounds and have been widely used in various industrial fields for decades. They are known to be environmentally persistent. Thus far numerous reports have been focused on reproductive toxicity of PFAs in animals but few studies have been carried out on toxicity towards human cells.

Preliminary studies focused on estimation of EC₅₀ values by viability tests performed at varying time-exposures on CF₆-CF₁₈ PFAs with human colon carcinoma (HCT116) cells. Cytotoxicity increased with the elongation of fluorocarbon chain length (PFHxA>PFHpA>PFOA>PFNA>PFDA>PFDoA>PFTeDA) while higher lipophilicity (CF₁₆ and CF₁₈) did not deepen the effect but even partially reversed it. The effect was intensified after longer exposure (72 h); at relatively low 40 μM PFTeDA, the viability decreased to ~50%.

Comparative mechanistic analysis with 200 μM perfluorodecanic acid [PFDA] and its natural analogue as a reference – decanoic acid [DA] were carried out in time-dependent manner by GC-MS and flow cytometry, respectively. PFDA after 4 h caused visible loss of cell transmembrane potential up to 42% comparing with 12% for DA. Following exposures (24 - 72h), particularly with PFDA, revealed significant disorders in downstream events as dissipation of mitochondrial transmembrane potential (ΔΨ_m), H₂O₂ and ^·O₂^- generation, cytochrome c release and activation of caspase 9 and -3. In order to evaluate the importance of functional mitochondria in PFDA-induced apoptosis, cells were co-treated with PFDA and inhibitor of mitochondrial transition pore (MPT) - Cyclosporin A (CsA). Presence of CsA reduced ΔΨ_m dissipation, cytochrome c release and apoptotic fragmentation of nuclear DNA, indicating a role for PFDA-induced apoptosis dependent on the mitochondrial intrinsic pathway.

We claim that more pronounced and longer lasting PFAs effects compared with natural acids on cultured cells may have similar mechanism of action.

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